DESCRIPTION (Verbatim from Applicant's Abstract): Sudden cardiac death accounts for approximately 400,000 deaths each year in the United States and remains a health problem of epidemic proportions. Most sudden cardiac deaths are caused by fatal ventricular arrhythmias. An effort aimed at the primary prevention of sudden cardiac death requires efficient identification of patients who are at high enough risk for having these arrhythmias to warrant aggressive prophylactic therapy. A number of recently completed, randomized clinical trials have demonstrated that an implantable cardiac defibrillator (ICD) can prevent sudden cardiac death in a highly selected group of high-risk patients. When these trials are viewed together, the only patients in whom the prophylactic implantation of an ICD has proven benefit are those patients identified by documented, spontaneous or inducible, sustained ventricular arrhythmias. Two randomized treatment trials (MADIT II, SCD-HEFT) are currently testing the hypothesis that implantation of an ICD will reduce mortality in patients with congestive heart failure (CHF) and left ventricular dysfunction without any further risk stratification. However, the implications of these two trials-implantation of an ICD in every patient with CHF-are unlikely to be accepted either by the medical community or by health care payers. More efficient methods of risk stratification will be necessary to identify those patients with CHF who are most likely to benefit from prophylactic treatment with an ICD. It has recently been shown that T Wave Alternans (TWA) measured during exercise is strongly associated with inducible monomorphic CVT and with subsequent spontaneous arrhythmic events. This preliminary data suggest that TWA may be an efficient and non-invasive surrogate for electrophysiologic testing to screen patients who may be at high-risk for sudden cardiac death. The purpose of this study is to evaluate the prognostic significance of TWA in a prospective epidemiologic natural history study. Ultimately, the planning of a randomized treatment trial that utilizes TWA in some combination with other risk factors to select patients at high-risk for sudden cardiac death requires answers to a number of questions from an unbiased natural history study. What is the magnitude of the increase in risk of having an arrhythmic event if TWA is present? Is the increase in risk similar for those patients with ischemic and non-ischemic cardiomyopathy? What is the relationship between TWA and the other risk factors (EF, NSVT, and RR variability)? Is the association between TWA and arrhythmic events independent of these other risk factors? What is the most clinically efficient method of combining risk factors to identify a group of patients at high-risk for having an arrhythmic event? The research described in this grant application will provide the data necessary to answer these questions.